The specific pathogenic processes underlying periodontal diseases have not yet been elucidated. Anaerobic bacteria present in the periodontal pockets have been suspected to play a role in disease initiation and progression, and numerous studies have focused on the immune responses involved. Here, we sought to establish whether these bacteria might contain superantigens, substances capable of stimulating an entire class of T-cells to respond and proliferate in a relatively non-specific manner. We assessed this by exposing cultured peripheral blood cells to sonicates of the candidate bacteria as well as to control substances known to induce superantigen responses such as toxic shock syndrome toxin. We assessed whether the bacteria were inducing a superantigen response by measuring the amount of T-cell m-RNA of each of 20 V-beta classes using a RT-PCR method. Our data indicate that these microbes do contain superantigens, but the level of response may differ among different human subjects. This, in turn, supports the hypothesis that human genetic variation may play an important role in susceptibility to periodontal diseases.